Menaces humaines et microbiennes : résistance aux antimicrobiens, mortalité et infections émergentes

Depuis une dizaine d’années, le sujet de la résistance aux antimicrobiens nous menace. Toutes les études menées aux instituts de recherche sont faites afin d’évaluer le chiffre réel de la résistance aux antibiotiques et la mortalité liée à cette résistance. Les scientifiques, les journalistes et les médias ont joué un rôle dans la diffusion de plusieurs rapports apocalyptiques et alarmistes concluant à un surplus de 10 millions de décès relatifs à des infections résistantes aux antimicrobiens en 2050. Ces rapports étaient pour la plupart fondés sur des modèles mathématiques et une collecte de données inexactes, plutôt que sur des preuves réelles. La clé de la préparation et des mesures d'urgence réside dans la surveillance épidémiologique en temps réel, qui permet de recueillir des preuves, d'analyser les données et de détecter les tendances nouvelles, émergentes ou réapparues. Alors, notre crainte de mourir de la résistance aux antimicrobiens est-elle justifiée ? Je concentre ma thèse sur cette polémique à travers : 1) La surveillance et l'analyse des tendances de la résistance aux médicaments antimicrobiens nosocomiaux des isolats cliniquement importants (E. coli, K. pneumoniae , P. aeruginosa , A. baumannii , S. aureus , and E. faecium ) au CHU Saint Georges au Liban de 2010 à 2020, 2) Déterminer l'épidémiologie locale et comprendre les mécanismes de la résistance aux médicaments antimicrobiens et sa relation avec la consommation d'antimicrobiens, 3) Explorer la controverse de la résistance aux antimicrobiens et de la mortalité attribuable, ses défis et le statu quo réel de la résistance aux médicaments bactériens et de la mortalité.The fear of antimicrobial resistance looms over us for the past decade. Scientists, journalists, and the media played a role in the spread of several apocalyptic reports and exaggerations concluding that 10 million excess deaths due to antimicrobial resistant infections are to be expected in 2050. These reports were mostly based on mathematical models and inaccurate data collection, rather than real evidence. The key to readiness and emergency preparedness lies in epidemiologic, real-time surveillance to gather evidence, analyze data, and detect new, emerging, or remerging patterns. So, is our fear of dying from antimicrobial resistance justified? I focus my thesis on addressing this modern-day polemic through: 1) Surveillance and trend analysis of nosocomial antimicrobial drug resistance of clinically important isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus , and Enterococcus faecium ) at Saint George Hospital University Medical Center, Lebanon from 2010 to 2020, 2)Determining the local epidemiology and insight into the mechanisms of antimicrobial drug resistance and its relation to antimicrobial consumption, 3)Mapping Emerging Infections and their subsequent outbreaks, and 4)Exploring the controversy of antimicrobial resistance and attributable mortality, its challenges and the real status quo of bacterial drug resistance and mortality

Draft Genome Sequences of Two Multidrug-Resistant Sequence Type 405 Escherichia coli Isolates without Clinical Infection

International audienceWe present the genome sequences of two carbapenemase-producing sequence type 405 Escherichia coli clinical isolates, strains Marseille-Q1950 and Marseille-Q1951. The isolates were obtained 1 month apart during the patient’s hospitalization in Lebanon, in May (Marseille-Q1950) and June (Marseille-Q1951) 2019. The genome sizes of strains Marseille-Q1950 and Marseille-Q1951 were 5,181,515 bp and 5,213,451 bp, respectively

Draft Genome Sequence of an NDM-1-Producing Sequence Type 101 (ST101) Klebsiella pneumoniae Strain, Marseille-Q1949

International audienceA pan-drug-resistant Klebsiella pneumoniae strain was isolated from the blood of a 70-year-old critically ill patient in April 2019. Interestingly, the patient recovered and was discharged home a month later. The genome of strain Marseille-Q1949 is 5,607,584-bp long and has a 57.1% G+C content and 5,467 protein-coding genes

First Detection of Colistin-Resistant Klebsiella pneumoniae in Association with NDM-5 Carbapenemase Isolated from Clinical Lebanese Patients

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SCA Medium: A New Culture Medium for the Isolation of All Candida auris Clades

International audienceCandida auris is an emerging multidrug-resistant yeast causing nosocomial infections and associated with high mortality in immunocompromised patients. Rapid identification and characterisation are necessary for diagnosis and containing its spread. In this study, we present a selective culture medium for all C. auris clades. This medium is sensitive with a limit of detection ranging between 101 and 102 CFU/mL. The 100% specificity of SCA (specific C. auris) medium is confirmed on a set of 135 Candida strains, 50 bacterial species and 200 human stool samples. Thus, this medium specifically selects for C. auris isolation from clinical samples, allowing the latter to study its phenotypic profile

The Effect of Decreased Antipseudomonal Drug Consumption on Pseudomonas aeruginosa Incidence and Antimicrobial Susceptibility Profiles over 9 Years in a Lebanese Tertiary Care Center

Pseudomonas aeruginosa (PAE) is intrinsically resistant to numerous classes of antimicrobials such as tetracycline and β-lactam antibiotics. More epidemiological surveillance studies on the antimicrobial susceptibility profiles of PAE are needed to generate clinically significant data and better guided therapeutic options. We describe and analyze in a retrospective study the epidemiologic trends of 1827 Pseudomonas spp. isolates (83.5% PAE, 16.4% Pseudomonas sp., and 0.2% Pseudomonas putida) from various clinical specimens with their resistance patterns to antimicrobial consumption at a tertiary medical center in Lebanon between January 2010 and December 2018. We report a significant drop in the incidence of PAE from sputum (p-value = 0.05), whereas bloodstream infection isolation density showed no trend over the study period. We also registered a minimal but statistically significant drop in resistance of Pseudomonas to certain antibiotics and a decrease in the consumption of antipseudomonal antibiotics (p-value < 0.001). Only 61 PAE isolates from a total of 1827 Pseudomonas cultures (3.33%) were difficult to treat, of which only one was a bacteremia. Interestingly, we found that the carbapenem susceptibility of Pseudomonas was unaffected by the decrease in their consumption. These results augur that antimicrobial pressure may not be the sole contributor to resistance emergence. Finally, antimicrobial stewardship seems to have a positive impact on nosocomial epidemiology

The Effect of Decreased Antipseudomonal Drug Consumption on <i>Pseudomonas aeruginosa</i> Incidence and Antimicrobial Susceptibility Profiles over 9 Years in a Lebanese Tertiary Care Center

Pseudomonas aeruginosa (PAE) is intrinsically resistant to numerous classes of antimicrobials such as tetracycline and β-lactam antibiotics. More epidemiological surveillance studies on the antimicrobial susceptibility profiles of PAE are needed to generate clinically significant data and better guided therapeutic options. We describe and analyze in a retrospective study the epidemiologic trends of 1827 Pseudomonas spp. isolates (83.5% PAE, 16.4% Pseudomonas sp., and 0.2% Pseudomonas putida) from various clinical specimens with their resistance patterns to antimicrobial consumption at a tertiary medical center in Lebanon between January 2010 and December 2018. We report a significant drop in the incidence of PAE from sputum (p-value = 0.05), whereas bloodstream infection isolation density showed no trend over the study period. We also registered a minimal but statistically significant drop in resistance of Pseudomonas to certain antibiotics and a decrease in the consumption of antipseudomonal antibiotics (p-value < 0.001). Only 61 PAE isolates from a total of 1827 Pseudomonas cultures (3.33%) were difficult to treat, of which only one was a bacteremia. Interestingly, we found that the carbapenem susceptibility of Pseudomonas was unaffected by the decrease in their consumption. These results augur that antimicrobial pressure may not be the sole contributor to resistance emergence. Finally, antimicrobial stewardship seems to have a positive impact on nosocomial epidemiology

Control and Elimination of Extensively Drug-Resistant Acinetobacter baumanii in an Intensive Care Unit

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Epidemiological Description and Detection of Antimicrobial Resistance in Various Aquatic Sites in Marseille, France

International audienceAntibiotic resistance is a worldwide public health concern and has been associated with reports of elevated mortality. According to the One Health concept, antibiotic resistance genes are transferrable to organisms, and organisms are shared among humans, animals, and the environment. Consequently, aquatic environments are a possible reservoir of bacteria harboring antibiotic resistance genes. In our study, we screened water and wastewater samples for antibiotic resistance genes by culturing samples on different types of agar media. Then, we performed real-time PCR to detect the presence of genes conferring resistance to beta lactams and colistin, followed by standard PCR and gene sequencing for verification. We mainly isolated Enterobacteriaceae from all samples. In water samples, 36 Gram-negative bacterial strains were isolated and identified. We found three extended-spectrum β-lactamase (ESBL)-producing bacteria—Escherichia coli and Enterobacter cloacae strains—harboring the CTX-M and TEM groups. In wastewater samples, we isolated 114 Gram-negative bacterial strains, mainly E. coli, Klebsiella pneumoniae, Citrobacter freundii and Proteus mirabilis strains. Forty-two bacterial strains were ESBL-producing bacteria, and they harbored at least one gene belonging to the CTX-M, SHV, and TEM groups. We also detected carbapenem-resistant genes, including NDM, KPC, and OXA-48, in four isolates of E. coli. This short epidemiological study allowed us to identify new antibiotic resistance genes present in bacterial strains isolated from water in Marseille. This type of surveillance shows the importance of tracking bacterial resistance in aquatic environments

Trends of Multidrug-Resistant Pathogens, Difficult to Treat Bloodstream Infections, and Antimicrobial Consumption at a Tertiary Care Center in Lebanon from 2015–2020: COVID-19 Aftermath

International audienceIntroduction: We studied the trend of antimicrobial resistance and consumption at Saint George Hospital University Medical Center (SGHUMC), a tertiary care center in Beirut, Lebanon, with a focus on the SARS-CoV-2 pandemic. Materials and Methods: We calculated the isolation density/1000 patient-days (PD) of the most isolated organisms from 1 January 2015–31 December 2020 that included: E. coli (Eco), K. pneumoniae (Kp), P. aeruginosa (Pae), A. baumannii (Ab), S. aureus (Sau), and E. faecium (Efm). We considered March–December 2020 a surrogate of COVID-19. We considered one culture/patient for each antimicrobial susceptibility and excluded Staphylococcus epidermidis, Staphylococcus coagulase-negative, and Corynebacterium species. We analyzed the trends of the overall isolates, the antimicrobial susceptibilities of blood isolates (BSI), difficult-to-treat (DTR) BSI, carbapenem-resistant Enterobacteriaceae (CRE) BSI, and restricted antimicrobial consumption as daily-defined-dose/1000 PD. DTR implies resistance to carbapenems, beta-lactams, fluoroquinolones, and additional antimicrobials where applicable. Results and Discussion: After applying exclusion criteria, we analyzed 1614 blood cultures out of 8314 cultures. We isolated 85 species, most commonly Eco, at 52%. The isolation density of total BSI in 2020 decreased by 16%: 82 patients were spared from bacteremia, with 13 being DTR. The isolation density of CRE BSI/1000 PD decreased by 64% from 2019 to 2020, while VREfm BSI decreased by 34%. There was a significant decrease of 80% in Ab isolates (p-value < 0.0001). During COVID-19, restricted antimicrobial consumption decreased to 175 DDD/1000 PD (p-value < 0.0001). Total carbapenem consumption persistently decreased by 71.2% from 108DDD/1000 PD in 2015–2019 to 31 DDD/1000 PD in 2020. At SGHUMC, existing epidemics were not worsened by the pandemic. We attribute this to our unique and dynamic collaboration of antimicrobial stewardship, infection prevention and control, and infectious disease consultation